This invention relates to novel intermediates useful in the preparation of 3,4-dihydro-5-methyl-6-(2-methylpropyl)-4-oxothieno[2,3-d]pyrimdine-]-carb oxylic acid (tiprinast) and related compounds. This invention also relates to the regioselective synthesis of such intermediates.
Tiprinast, which has the formula ##STR4## and related compounds are useful as orally active antiallergy agents. The preparation of tiprinast and related compounds is described in U.S. Pat. Nos. 4,054,656 and 4,159,377 to Davis L. Temple, Jr., the disclosures of which are incorporated herein by reference. Esters of tiprinast and related compounds, which are also useful as orally active antiallergy agents, are disclosed in an article by D. L. Temple et al, J. Med. Chem., Volume 22, pages 505-510 (1979), the disclosure of which is incorporated herein by reference. The basic approach to these compounds has been to construct the pyrimidinone ring on a 2-amino-3-carboxy substituted thiophene, which in turn is available from procedures published by K. Gewald et al in Chem. Ber., 99, pages 94-100 (1966). However, the Gewald et al procedures result in a mixture of 2-aminothiophene-3-carboxylate isomers which are not easily separated. The present invention permits the use of this mixture of isomers without separation.